Relative contributions of G protein, channel, and receptor to voltage-dependent inhibition of neuronal N-type and P/Q-type calcium channels in HEK 293 cell lines.
The voltage-dependent modulation of neuronal voltage-gated calcium channels by heterotrimeric G protein-coupled receptors potentially provides a means for activity-dependent modulation of synaptic efficacy. Recent attention has focused upon the molecular mechanisms by which such G proteins influence the biophysical properties of calcium channels. We have used an HEK 293-based heterologous system which stably expresses human neuronal calcium channels to address the relative contributions of receptor, G protein, and channel to voltage-dependent inhibition. We find that the receptor and channel subtype only insignificantly influence the time it takes to re-establish modulation following voltage-dependent relief of inhibition. In contrast, the G protein subtype mediating inhibition appears to play a significant part in this process. These results emphasize the importance of G protein subtype in the modulation of neuronal calcium channels.
McCool
B A
BA
Department of Medical Pharmacology and Toxicology, Texas A and M University Health Science Center, College Station 77843-1114, USA. mccool@medicine.tamu.edu
Harpold
M M
MM
Stauderman
K A
KA
Brust
P F
PF
Lovinger
D M
DM
D015220:Calcium Channels / Q000145:classification / Q000502:physiology*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015398:Signal Transduction; D009435:Synaptic Transmission; D014162:Transfection
D015220:Calcium Channels; D018094:Receptors, Metabotropic Glutamate; D019204:GTP-Binding Proteins